Polysaccharide Conjugate Research Articles

Physicochemical stability of Pickering emulsion stabilised by green tea polysaccharide conjugates‐soy protein isolate complex and its delivery of curcumin

SummaryTea processing often generates significant waste, resulting in resource inefficiency. However, extracting green tea polysaccharide conjugate (gTPC) from this waste has shown promising bioactivity. Previous studies have confirmed the emulsifying properties of gTPC. Yet, its use as an emulsifier is limited due to its requirement for high surface activity. The findings revealed that a 0.40 wt% soy protein isolate (SPI) and 0.50 wt% gTPC conjugate required 300 °C for complete decomposition, demonstrating the highest stability among other ratios. The Pickering emulsion, using a 0.30 wt% emulsifier ratio, exhibited exceptional stability. Moreover, it showed remarkable zeta potential and particle size stability under stressful conditions (temperature, pH and metal ions). Additionally, it effectively protected curcumin from adverse pH, light and temperature effects, with a retention rate of over 74.00%. These results highlight the gTPC/SPI combination as an effective stabiliser, offering new prospects for gTPC development and utilisation.

In vivo functional immunoprotection correlates for vaccines against invasive bacteria

Vaccination has significantly reduced the incidence of invasive infections caused by several bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. However, no vaccines are available for many other invasive pathogens. A major hurdle in vaccine development is the lack of functional markers to quantify vaccine immunity in eliminating pathogens during the process of infection. Based on our recent discovery of the liver as the major organ of vaccine-induced clearance of blood-borne virulent bacteria, we here describe a new vaccine evaluation system that quantitatively characterizes the key features of effective vaccines in shuffling virulent bacteria from the blood circulation to the liver resident macrophage Kupffer cells (KCs) and sinusoidal endothelial cells (LSECs) in mouse septic infection model. This system consists of three related correlates or assays: pathogen clearance from the bloodstream, pathogen trapping in the liver, and pathogen capture by KCs/LSECs. These readouts were consistently associated with the serotype-specific immunoprotection levels of the 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against lethal infection of S. pneumoniae, a major invasive Gram-positive pathogen of community-acquired infections in humans. Furthermore, the reliability and sensitivity of these correlates in reflecting vaccine efficacy were verified with whole cell vaccines of Klebsiella pneumoniae and Escherichia coli, two major Gram-negative pathogens in hospital-acquired invasive infections. This system may be used as effective readouts to evaluate the immunoprotective potential of vaccine candidates in the preclinical phase by filling the current technical gap in vaccine evaluation between the conventional in vitro approaches (e.g. antibody production and pathogen neutralization/opsonophagocytosis) and survival of immunized animals.

Ten-year analysis of the efficacy of vaccination against pneumococcal infection in patients with chronic obstructive pulmonary disease

Major problems in the course of chronic obstructive pulmonary disease (COPD) include frequent exacerbations and related deaths. The use of pneumococcal vaccines, primarily a 13-valent polysaccharide conjugate vaccine, is a generally recognized tool for reducing the number of exacerbations.The aim of the study was to analyze the prospective clinical efficacy of vaccine prophylaxis with conjugated pneumococcal vaccine Prevenar-13 (PCV13) in patients with COPD over 10 years.Methods. A total of 362 male patients who were treated or monitored at the Regional Pulmonological Center of Chelyabinsk in 2012 – 2022 were enrolled in the study. The main efficacy endpoints of observation over 10 years were: the dynamics of dyspnea (mMRC score), forced expiratory volume in 1st second, the number of exacerbations, hospitalizations, the number of pneumonias. After confirming the diagnosis of COPD, the patients were divided into two observation groups. The first group (n = 150) included patients vaccinated with PCV13. The second group (n = 212) included patients with COPD who had not received pneumococcal vaccination for various reasons.Results. Severe forms of the disease and frequent exacerbations predominated in both groups. 96 (27%) deaths were recorded in the PCV13-vaccinated group, and 171 (47%) deaths in the unvaccinated group. The difference between vaccinated and unvaccinated is statistically significant (p < 0.05). In the unvaccinated patients, there was a steady progression of shortness of breath with an increase by 12% compared to baseline (p < 0.05) by the 10th year. A positive trend in FEV1 was noted in patients vaccinated with PCV13. They also showed a significant decrease in BODE prognostic index.Conclusion. The use of PCV13 allows for stabilization of the main clinical and functional indicators of the respiratory system in patients with COPD in the long term (at least 10 years of follow-up). Vaccination maintains a low risk of adverse events according to the BODE index; an increase in patient survival was noted over a 10-year horizon (odds ratio – 2.35; 95% confidence interval – 1.45; 3.77), including cases with acute viral damage with COVID-19 (COronaVIrus Disease 2019).

Green tea polysaccharide conjugates and bovine serum albumin have a synergistic effect in improving the emulsification ability

Our previous study revealed that green tea polysaccharide conjugate (gTPC) has emulsion effect, but its emulsifying ability is weak. In order to improve the emulsification ability of gTPC, gTPC and bovine serum albumin (BSA) were combined to form five different mass proportions of the TPC/BSA (TB) complex: TPC/BSA: 5:1, 5:2, 5:3, 5:4, and 5:5 w/w. We observed that the 5:5 w/w TB emulsion was more hydrophobic and surface-active. Furthermore, the emulsions prepared using 50.00wt% medium-chain triglycerides exhibited the best stability. In addition, the TB emulsion exhibited stability in adverse environments of pH, salt, and heat; in particular, under salt conditions, no significant changes were observed in zeta potential. Subsequently, in vitro simulated digestion experiments were performed to investigate the use of TB emulsions for β-carotene encapsulation. We observed that the encapsulation efficiency for β-carotene was approximately 90.0%; it was subsequently released in the intestine.

Effectiveness of 13-valent pneumococcal conjugate vaccine against invasive disease caused by serotype 19A in children: a meta-analysis

Objective: Using Meta-analysis to evaluate the vaccine effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against invasive Streptococcus pneumoniae disease (IPD) caused by serotype 19A in children <5 years old. Methods: "Streptococcus pneumoniae infection""invasive pneumococcal disease""13-valent pneumococcal polysaccharide conjugate vaccine""PCV13""effectiveness""infant""child" and related terms were searched from China National Knowledge Infrastructure (CNKI), WANFANG DATA, PubMed, SCOPUS and Web of science with no limited on language, region and research institution. The retrieval time was limited from January 2010 to February 2023 and cohort study, case-control study and randomized controlled trial were included. Data were extracted from eligible studies by two independent reviewers, and after study quality assessment by NOS scale, Meta-analysis was completed using Stata 16.0 software. Results: A total of 2 340 related literatures were searched, and 10 literatures were finally included, including 5 case-control studies and 5 indirect cohort studies, which showed good literature quality. The vaccine effectiveness against serotype 19A IPD of PCV13 in children was 83.91% (95%CI: 78.92%-88.89%), and the subgroup analysis (P=0.240) showed there was no significant difference among the case-control study (VE=87.34%, 95%CI:79.74%-94.94%) and the indirect cohort study (VE=81.30%, 95%CI:74.69%-87.92%). The funnel plot and Egger test suggested that the possibility of publication bias was small. Conclusion: The present evidence indicates that PCV13 has a good vaccine effectiveness against serotype 19A IPD in children, and it is recommended to further increase the vaccination rate of PCV13 to reduce the disease burden of IPD in children <5 years old.

Propositive follow-up: Long-term immune responses to the 4CMenB and MenACWY vaccines in people living with HIV.

People living with HIV have an increased risk of meningococcal disease. The Propositive trial evaluated co-administration of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in people with HIV. The follow-up trial assessed the immunogenicity of these vaccines at 1.5 and 2.5 years after primary vaccination. Participants who completed the parent Propositive trial were invited to the follow-up study. Immunogenicity analysis was performed at 18 and 30 months after primary vaccination. Primary outcome measures were serum bactericidal antibody (SBA) geometric mean titres (GMTs) against three MenB reference strains and the proportion of participants maintaining a protective SBA titre of ≥4 at 18 and 30 months. Secondary outcome measures were SBA GMTs against MenA, C, W, and Y serogroups and the proportion of participants maintaining a protective SBA titre of ≥8 at 18 and 30 months. The trial is registered with Clinicaltrials.gov (NCT042394300). A total of 40 participants aged 22-47 years were enrolled. Geometric mean titres waned by 18 and 30 months but remained higher than pre-vaccination for all MenB strains and MenA, C, W, and Y. In total, 75%-85% of participants retained protective SBA titres by 30 months against individual MenB strains, whereas 68.8% of patients retained protective antibody titres against all three MenB strains. Antibodies against MenC waned more rapidly than did those against MenA, W, and Y. The proportion of participants with protective titres against MenC at 30 months was also lower (46.9%) than that with protective titres against MenA (87.5%), W (78.1%), and Y (87.5%). Immune responses against MenB in our cohort of people living with HIV at 2.5 years of follow-up were reassuring, with 68.8% of participants retaining protection against all three reference strains. However, responses against MenC were lower than those against MenA, W, and Y serogroups.

Changes in emulsifying properties of caseinate–Soy soluble polysaccharides conjugates by ultrasonication

This research aimed to assess the impact of ultrasonication on the emulsifying ability of a conjugate system composed of sodium caseinate and soluble soy polysaccharides. The study analyzed the characteristics of the particles and evaluated the emulsions produced using nanoconjugates. The results showed that ultrasonication improved the contact angle (63.7°) and decreased particle size (75 nm), resulting in more effective emulsifying efficiency. At a 2 % concentration of the nanoconjugates, stable emulsions with a 50 % oil content were successfully formed through complete coverage of the droplets' surface, and no oil release was observed. Moreover, the emulsions’ creaming index remained below 25 % even after 60 days of storage. The stability of the nanoconjugate-based emulsions depended on the concentration of nanoconjugates, with an optimal concentration of 4 %. These findings suggest that the nanoconjugates have great potential as a natural stabilizer for emulsion-based products.

The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi

Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into “Metabolic genotypes” (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.

A new candidate epitope-based vaccine against PspA PhtD of Streptococcus pneumoniae: a computational experimental approach.

Pneumococcus is an important respiratory pathogen that is associated with high rates of death in newborn children and the elderly. Given the disadvantages of current polysaccharide-based vaccines, the most promising alternative for developing improved vaccines may be to use protein antigens with different roles in pneumococcus virulence. PspA and PhtD, highly immunogenic surface proteins expressed by almost all pneumococcal strains, are capable of eliciting protective immunity against lethal infections. In this study using immunoinformatics approaches, we constructed one fusion construct (called PAD) by fusing the immunodominant regions of PspA from families 1 & 2 (PA) to the immunodominant regions of PhtD (PD). The objective of this project was to test the immunogenicity of the fusion protein PAD and to compare its protective activity against S. pneumoniae infection with PA or PD alone and a combination of PA and PD. The prediction of physicochemical properties, antigenicity, allergenicity, toxicity, and 3D-structure of the constructs, as well as molecular docking with HLA receptor and immune simulation were performed using computational tools. Finally, mice were immunized and the serum levels of antibodies/cytokines and functionality of antibodies in vitro were evaluated after immunization. The mice survival rates and decrease of bacterial loads in the blood/spleen were examined following the challenge. The computational analyses indicated the proposed constructs could be antigenic, non-allergenic, non-toxic, soluble and able to elicit robust immune responses. The results of actual animal experiments revealed the candidate vaccines could induce the mice to produce high levels of antibodies and cytokines. The complement-mediated bactericidal activity of antibodies was confirmed and the antibodies provided favorable survival in immunized mice after bacterial challenge. In general, the experimental results verified the immunoinformatics studies. For the first time this report presents novel peptide-based vaccine candidates consisting of immunodominant regions of PspA and PhtD antigens. The obtained findings confirmed that the fusion formulation could be relatively more efficient than the individual and combination formulations. The results propose that the fusion protein alone could be used as a serotype-independent pneumococcal vaccine or as an effective partner protein for a conjugate polysaccharide vaccine.

Evaluating clinical effectiveness and safety of pneumococcal immunization of infants

According to WHO, pneumococcal infection (PI) is considered one of the most dangerous of all vaccine-preventable diseases and, before vaccination, led to the death of up to 1.6 million people per year, of which from 0.7 to 1 million were children. In the prevention of PI, specific prevention occupies a special place. For the first time in 2014, vaccination against PI with pneumococcal conjugate vaccine was included in the national calendar of preventive vaccinations. International practice of using pneumococcal vaccine has shown that timely vaccination can produce positive results in the fight against PI. Under observation were 55 children who were vaccinated against PI with the pneumococcal polysaccharide conjugate vaccine (adsorbed), 13 valent according to the national calendar of preventive vaccinations of the Russian Federation. It was revealed that post-vaccination complications after vaccination did not occur in any child. General post-vaccination reactions were observed in the form of a short-term increase in temperature, loss of appetite and sleep disturbances, as well as local reactions in the form of edema, hyperemia, and hardening at the site of vaccine administration. We studied the incidence of community-acquired pneumonia (CAP), acute otitis media and acute respiratory infections among 55 children of the first year of life vaccinated at 2 months and 4.5 months (main group) and 50 children for various reasons not vaccinated against PI (comparison group). A study of the long-term results of 2-fold vaccination in the first year of life and revaccination at 15 months against PV based on observation of children for two years showed that children of the main group, compared with the comparison group, were 3.3 times less likely to suffer from PV, 2.7 times acute otitis and 1.7 times acute respiratory infections, p &lt; 0.05. The data obtained show the high efficiency and safety of vaccinating children against PI with the pneumococcal vaccine.

Antioxidant stability and in vitro digestion of β-carotene-loaded oil-in-water emulsions stabilized by whey protein isolate-Mesona chinensis polysaccharide conjugates

The aim of this study was to investigate the delivery of functional factor β-carotene by emulsion stabilized with whey protein isolate-Mesona chinensis polysaccharide (WPI-MCP) conjugate. Results showed that the WPI-MCP complex had better antioxidant properties than WPI. Correspondingly, the emulsions stabilized by this complex also had better oxidative stability compared with protein emulsions alone. The particle size of WPI-MCP emulsion was smaller and had a better stability when MCP was added at 0.2 % (w/v). The sizes of WPI-MCP and WPI emulsions were 3594.33 and 7765.67 nm at pH 4, indicating improved emulsion stability around isoelectric point of WPI. At different NaCl concentrations, the absolute values of zeta-potential of WPI-MCP emulsions were larger than that of WPI emulsions except 0.1 % (mol/L) NaCl. The sizes of WPI and WPI-MCP emulsions were 2384.32 and 790.12 nm, respectively. During in vitro digestion, WPI-MCP stabilized emulsions slowed down the release of free fatty acids and achieved about 80 % bioaccessibility of β-carotene, indicating that WPI-MCP-stabilized emulsions encapsulating β-carotene can effectively control the release of bioactive substances. These studies have potential significance and value for the construction of food-grade emulsion delivery system.

High-internal-phase emulsions stabilized by alkali-extracted green tea polysaccharide conjugates for curcumin delivery

Exploring the emulsification capabilities of tea polysaccharide conjugates (TPCs) in high-internal-phase emulsions (HIPEs) would further expand the utilization value of TPCs. This study aimed to prepare 0.1–0.5 wt% alkali-extracted green tea polysaccharide conjugate (gTPC-A)-stabilized HIPEs containing 75–87 wt% medium chain triglycerides (MCTs) to investigate their stability, rheology, microstructure, and loading and protective effects on curcumin. The findings revealed that only 0.1 wt% of gTPC-A could stabilize HIPEs containing 85 wt% oil for 30 days. HIPEs had better storage stability in a weakly acidic environment at pH 5.0–6.0 and at temperatures less than 70 °C. HIPEs could load curcumin and protect it from ultraviolet (UV) radiation and in vitro digestion. The half-life of curcumin loaded in HIPEs was 65 h under UV radiation. The curcumin bioaccessibility of HIPEs (56.29 %) was higher than that in MCT (8.73 %). These results provided a theoretical basis for the extensive use of TPCs.

Promising pharmaceutical development of vaccines for the prevention of meningococcal infection

Meningococcal infection (MI) refers to anthroponoses; is an acute infectious disease with an aerosol transmission mechanism, characterized by various forms of the infectious process: from local (nasopharyngitis) and asymptomatic infections to generalized forms of invasive infection with the development of meningococcemia and meningitis. The causative agent of MI is meningococcus (Neisseria meningitidis) that belongs to the pathogen risk group 2. Preventive vaccination against MI is included in the calendar of preventive vaccinations according to epidemic indications. The problem of MI retains a great medical and social significance for Russian health care due to the continuing high rates of associated mortality, disability, high costs of treatment and rehabilitation. Vaccines against five of the six main N. meningitidis serogroups have been registered worldwide. Serogroup X vaccine is under development. Recently, there has been an increase in the heterogeneity of the meningococcal population due to serogroups W, Y, and X. The polysaccharide vaccines developed in Russia have restrictions on their use, and there is no full-cycle production of meningococcal conjugate vaccines in the Russian Federation. Given the above, the development and registration of new vaccines against MI is an urgent task.&#x0D; The purpose of this work is to analyze the current state of development of vaccines for MI prevention. Currently, depending on the production technology, the following types of meningococcal vaccines are available: polysaccharide, conjugated, based on outer membrane vesicles (OMV), protein and based on synthetic polysaccharides. Serogroup-targeted meningococcal vaccines are effective in reducing the public health burden of invasive MI. Polysaccharide conjugate and protein/OMV vaccines are among the most promising vaccines for most invasive meningococcal serogroups. In modern conditions, with the progress in technologies for future polysaccharide conjugate vaccines, new opportunities are opening up for the use of such approaches as chemical/enzymatic synthesis, improved characteristics of the carrier protein, and site-specific conjugation. The development of a single vaccine against the main invasive meningococcal serogroups, rather than its individual antigenic variants, does not lose its relevance. It is timely to develop in the near future a vaccine against N. meningitidis serogroup X, which was previously a rare cause of sporadic meningitis, but has caused outbreaks in various African countries in 20062010 and in recent years.

Advances of Protein Functionalities Through Conjugation of Protein and Polysaccharide

Advances of Protein Functionalities Through Conjugation of Protein and Polysaccharide

Reinforcing alginate matrixes by tea polysaccharide conjugates or their stabilized nanoemulsion for probiotics encapsulation: Characterization, survival after gastrointestinal digestion and ambient storage

Tea polysaccharide conjugates (TPC) were used as fillers in the form of biopolymer or colloidal particles (TPC stabilized nanoemulsion, NE) for reinforcing alginate (ALG) beads to improve the probiotic viability. Results demonstrated that adding TPC or NE to ALG beads significantly enhanced the gastrointestinal viability of encapsulated probiotics when compared to free cells. Moreover, the survivability of free and ALG encapsulated probiotics markedly decreased to 2.03 ± 0.05 and 2.26 ± 0.24 log CFU/g, respectively, after 2 weeks ambient storage, indicating pure ALG encapsulation had no effective storage protective capability. However, adding TPC or NE could greatly enhance the ambient storage viability of probiotics, with ALG + NE beads possessing the best protection (8.93 ± 0.06 log CFU/g) due to their lower water activity and reduced porosity. These results suggest that TPC and NE reinforced ALG beads have the potential to encapsulate, protect and colonic delivery of probiotics.

Effect of hydrophobic property on antibacterial activities of green tea polysaccharide conjugates against Escherichia coli

We previously found that green tea polysaccharide conjugates (gTPCs) have antibacterial activity against Escherichia coli. In this study, the effect of hydrophobic property on the antibacterial activities of gTPCs was evaluated to elucidate their property-activity relationship. Three gTPCs (gTPCs-5 h, gTPCs-12 h and gTPCs-24 h) were extracted from green tea with the ethanol precipitation time of 5 h, 12 h and 24 h, respectively. These three gTPCs did not differ significantly in terms of molecular weight distribution, amino acids composition and zeta potentials. Fourier transform infrared spectroscopy results revealed that gTPCs-5 h and gTPCs-12 h processed more hydrogen bonds than gTPCs-24 h. The surface hydrophobicity and contact angle of gTPCs-5 h were larger than that of gTPCs-12 h and gTPCs-24 h. The antibacterial activity of gTPCs against E. coli decreased in the order of gTPCs-5 h > gTPCs-12 h > gTPCs-24 h. There wasn't significant difference among the zeta potentials of E. coli treated by gTPCs-5 h, gTPCs-12 h and gTPCs-24 h, but the bacterial contact angles of E. coli treated by gTPCs-5 h were higher compared with those of the other two gTPCs. Furthermore, gTPCs-5 h exhibited higher activity to decrease bacterial membrane proteins, and increase bacterial membrane permeability than the other two gTPCs. In conclusion, gTPCs with higher hydrophobicity property exhibited stronger antibacterial activity against E. coli.

Method development and validation of unbound saccharide content (serogroup A, C, Y, W, X) in novel pentavalent meningococcal polysaccharide conjugate vaccine with two different carrier proteins

Exclusive DOC-HCl formulations were developed for free polysaccharide content estimation in Meningococcal serogroup A, C, Y, W and X from pentavalent meningococcal vaccine (A, C, Y, W, X). The DOC precipitation method reported herein stands as an alternative to the ultra-filtration method for free polysaccharide estimation. DOC content was optimized for all the serogroups at a single concentration, where as effective acid concentration was altered as per serogroup. Briefly, two DOC-HCl formulations were developed for intended purpose, one for TT conjugated serogroups Men A & Men X where as other for CRM conjugated serogroups Men C, Men Y and Men W with effective HCl concentration of 23 mM and 193 mM for precipitation of Protein-DOC complex respectively. Furthermore, an exclusive buffer/DOC-HCl formulation for estimation of Men X free polysaccharide in fill finished product was developed. Accuracy of the method was proven at 12.5 %, 25 %, 50 % and 100 % of test specification where recoveries were found in the range of 70–130 %. In case of repeatability, intra assay variation ranged from 2 % to 7 % whereas inter assay variation was noted to be 2–14 %. Specificity studied revealed no interference of assay components such as sample excipients, DOC, acids. Critical quality and stability-indicating characteristics were measured. Monovalent polysaccharide standards of Men A, C, Y, W and X were developed and assigned the unitage concentration 1.01, 1.10, 1.09, 1.08 and 1.00 mg/mL respectively. Linearity curve was optimized from 0.17 to 27 µg/mL for Men A and C whereas from 0.33 to 27 µg/mL for Men Y and W considering free polysaccharide content estimation. The study suggests that DOC-HCl method meets all the criteria for free polysaccharide estimation in multivalent vaccines with additional advantages of high throughput and sized independent separation hence can be used for quality control testing.

Prognoses of patients undergoing hemodialysis administered 23-valent pneumococcal polysaccharide versus 13-valent pneumococcal protein conjugate vaccines

IntroductionSequential vaccination with the 13-valent pneumococcal protein conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients undergoing hemodialysis; however, evidence for the efficacy of these pneumococcal vaccines for patients undergoing hemodialysis is limited to a single dose. We aimed to evaluate the prognosis of patients undergoing hemodialysis who received vaccination with PPSV23 alone versus sequential vaccination with PCV13 and PPSV23. MethodsPatients undergoing hemodialysis who were vaccinated with PPSV23 alone (PPSV23 group) or PCV13 followed by PPSV23 (PCV13+PPSV23 group) between 2014 and 2016 were included; the observation period was three years from the first injection. Patients who underwent hemodialysis between 2011 and 2012 were included as controls. After propensity score matching using age, sex, dialysis vintage, diabetes history, pneumonia history, and serum albumin and creatinine levels, survival analysis was performed. ResultsThe study included 89, 71, and 319 patients in the PPSV23, PCV13+PPSV23, and control groups, respectively. After propensity score matching, the PPSV23 and control group 1 (79 patients each) and the PCV13+PPSV23 and control group 2 (61 patients each) were compared. Significant differences were observed in the survival rate between the PPSV23 group and control group 1 (p = 0.005) but not between the PCV13+PPSV23 group and control group 2. Pneumonia-related mortality in the two vaccinated groups did not differ significantly during the observation period. ConclusionsPatients who received PPSV23 had a favorable prognosis; however, no positive effect was demonstrated in the PCV13+PPSV23 group.

Safety and immunogenicity of a multivalent pneumococcal conjugate vaccine given with 13-valent pneumococcal conjugate vaccine in healthy infants: A phase 2 randomized trial

ABSTRACT Use of pneumococcal conjugate vaccines (PCVs) has led to substantial reductions in the global burden of pediatric pneumococcal disease. Expansion of serotype coverage has been achieved by increasing PCV valency, but this may carry the potential risk of antibody interference. A complementary 7-valent PCV (cPCV7) including polysaccharide conjugates from 7 non–13-valent (PCV13) serotypes was developed to potentially complement PCV13-mediated protection and expand serotype coverage. This study evaluated cPCV7 and PCV13 coadministered in separate limbs or separated in time in infants. This phase 2, multicenter, open-label study included 512 infants randomized 1:1:1 to receive cPCV7 coadministered with PCV13 at ages 2, 4, 6, and 12 months (cPCV7 Coadministered); cPCV7 given at ages 3, 5, 7, and 13 months, 3‒5 weeks after PCV13 (cPCV7 Separated); or PCV13 at ages 2, 4, 6, and 12 months followed by a single supplemental dose of cPCV7 at 13 months (PCV13 Control). Safety evaluations included local reactions, systemic events, and adverse events. Serotype-specific immunoglobulin G concentrations and opsonophagocytic activity titers were assessed. The safety profile of cPCV7 was similar to that of PCV13. cPCV7 was well-tolerated in infants when coadministered with or given separately from PCV13. Robust and functional immune responses for all cPCV7 serotypes were observed in both cPCV7 groups. No immunologic interference was observed for either the cPCV7 or PCV13 serotypes with coadministration. A single cPCV7 dose induced immune responses in toddlers. These findings support potential coadministration of a complementary PCV to supplement protection provided by existing PCVs. Trial registration: ClinicalTrials.gov, NCT03550313.

A combination of green tea polysaccharide conjugate and bovine serum albumin and its emulsion-stabilizing characteristics

Tea polysaccharide conjugates (TPC) and bovine serum albumin (BSA) have emulsifying properties, but they have certain shortcomings when used alone as emulsifiers. This study aimed to combine TPC and BSA to form a complex for applications to achieve the complementary advantages between them. The TPC/BSA complex was physicochemically characterized, and the results showed an improvement in its surface hydrophobicity. TPC/BSA emulsions with different concentrations (0.20–1.00 wt%) were prepared using TPC/BSA complex as the emulsifier. The effects of heat treatment, pH, and metal ions on the stability of TPC/BSA and BSA emulsions were investigated, and TPC/BSA emulsion systems loaded with epigallocatechin gallate (EGCG) and epigallocatechin (EGC) were constructed. TPC/BSA emulsion droplets were smaller than 1.00 wt% TPC emulsion droplets, and the particle size of 0.20 wt% TPC/BSA emulsion increased slightly during storage at 25 °C. Further, 0.20 wt% TPC/BSA emulsions became less stable after heat treatment, whereas the particle size of other concentrations did not change significantly after treatment at 70 ℃–90 °C. TPC/BSA emulsions were more stable at pH 6.0–9.0. Both were less affected by Na+, weakly affected by Ca2+ than BSA emulsion, and significantly affected by Al3+. TPC/BSA emulsion had a good protection effect on EGCG and EGC. The presence of EGCG and EGC improved the stability of the emulsion system, which remained stable for 90 days.